Bone cell activity responsive drug release from biodegradable apatite/collagen nano-composite cements--in vitro dissolution medium responsive vitamin K2 release.

A biodegradable drug delivery system with perforated macro pores was established using an apatite/collagen composite cement containing menatetrenone (VK2). The drug-release capabilities of the device were investigated in vitro under osteoblast and osteoclast-like conditions (SOB and SOC). A bulk powder of apatite cement containing 2.5% VK2 and 20% bovine collagen was obtained by grinding, kneaded with phosphoric acid, and poured into molds, producing fixed blocks with 0-60 perforated macro pores. The characteristics of these samples were measured by X-ray powder diffraction analysis and Fourier-transformed and infrared spectroscopy, and found to be very similar to those of natural bone. Drug release tests were performed under SOB in simulated body fluid (pH 7.8), and then under SOC in acetate buffer (pH 4.5) at 37.0±0.1 °C, and the process repeated twice. The device released almost no drug in SOB, but a significant amount in SOC. The drug release in SOC was not proportional to the number of macro pores in the first test, but was in the second. The device showed dissolution medium-responsive drug release.